Inhibition of monoamine oxidase B reduces atherosclerosis and fatty liver in mice
Open Access
- 3 January 2023
- journal article
- research article
- Published by Portland Press Ltd. in Clinical Science
- Vol. 137 (1), 17-30
- https://doi.org/10.1042/cs20220477
Abstract
Oxidative stress is vital for pathophysiology of atherosclerosis and non-alcoholic fatty liver disease (NAFLD). Monoamine oxidase (MAO) is an important source of oxidative stress in the vascular system and liver. However, the effect of MAO inhibition on atherosclerosis and NAFLD has not been explored. In this study, MAO A and B expressions were increased in atherosclerotic plaques in human and apolipoprotein E (ApoE)-deficient mice. Inhibition of MAO B (by deprenyl), but not MAO A (by clorgyline), reduced the atheroma area in the thoracic aorta and aortic sinus in ApoE-deficient mice fed the cholesterol-enriched diet for 15 weeks. MAO B inhibition attenuated oxidative stress, expression of adhesion molecules, production of inflammatory cytokines, and macrophage infiltration in atherosclerotic plaques and decreased plasma triglyceride and low-density lipoprotein (LDL) cholesterol concentrations. MAO B inhibition had no therapeutic effect on restenosis in the femoral artery wire-induced injury model in C57BL/6 mice. In the NAFLD mouse model, MAO B inhibition reduced lipid droplet deposition in the liver and hepatic total cholesterol and triglyceride levels in C57BL/6 mice fed high-fat diets for 10 weeks. Key enzymes for triglyceride and cholesterol biosynthesis (fatty acid synthase and 3-hydroxy-3-methylglutaryl-CoA reductase, HMGCR) and inflammatory markers were inhibited, and cholesterol clearance was upregulated (increased LDL receptor expression and reduced proprotein convertase subtilisin/kexin type 9, PCSK9, expression) by MAO B inhibition in the liver. These results were also demonstrated in the HepG2 liver cell model. Our data suggest that MAO B inhibition is a potential and novel treatment for atherosclerosis and NAFLDKeywords
This publication has 32 references indexed in Scilit:
- Monoamine oxidases are novel sources of cardiovascular oxidative stress in experimental diabetesCanadian Journal of Physiology and Pharmacology, 2015
- Monoamine Oxidases Are Mediators of Endothelial Dysfunction in the Mouse AortaHypertension, 2013
- Serotonin 5-HT2A receptor-mediated hypertrophy is negatively regulated by caveolin-3 in cardiomyoblasts and neonatal cardiomyocytesJournal of Molecular and Cellular Cardiology, 2012
- Behavioral outcomes of monoamine oxidase deficiency: preclinical and clinical evidenceInternational review of neurobiology, 2011
- The effect of selegiline on total scavenger capacity and liver fat content: a preliminary study in an animal modelJournal of Neural Transmission, 2011
- Monoamine Oxidase A–Mediated Enhanced Catabolism of Norepinephrine Contributes to Adverse Remodeling and Pump Failure in Hearts With Pressure OverloadCirculation Research, 2010
- A Spontaneous Point Mutation Produces Monoamine Oxidase A/B Knock-out Mice with Greatly Elevated Monoamines and Anxiety-like BehaviorOnline Journal of Public Health Informatics, 2004
- Impact of sustained deprenyl (selegiline) in levodopa‐treated Parkinson's disease: A randomized placebo‐controlled extension of the deprenyl and tocopherol antioxidative therapy of parkinsonism trialAnnals of Neurology, 2002
- Inhibition of human LDL oxidation by the neuroprotective drug l-deprenylNeurological Research, 2002
- Selegiline as the primary treatment of Parkinson's disease - a long-term double-blind studyActa Neurologica Scandinavica, 1997